Chinese Herbal Medicine Dingji Fumai Decoction for Ventricular Premature Contraction: A Real-World Trial.

BACKGROUND: Chinese herbal medicine Dingji Fumai Decoction (DFD) is widely clinically used for ventricular premature contraction (VPC). This real-word trial was designed to assess the safety and effectiveness of DFD for VPC. METHODS: This was a double-blinded, randomized placebo-controlled trial. Patients with VPC were randomized (1 : 1) to treatment with DFD combined with metoprolol (DFD arm) or metoprolol combined with placebo (MET arm). A primary end point was a composite of clinical symptoms and signs determined by the traditionalChinese medicine syndrome score and the number of VPC determined by the Holter examination. Second outcomes were adverse events, medication compliance, and laboratory examination. RESULTS: 144 patients were randomized to DFD arm (76 patients) or MET arm (68 patients), and 136 cases (71 in DFD arm and 65 in MET arm) finally completed this trial. After a 12-week follow-up, DFD arm significantly decreased traditional Chinese medicine syndrome score and the number of VPC compared with MET arm (P = 0.003 and 0.034, respectively). There was no adverse drug effect and patient medication compliance was good. CONCLUSIONS: Superiority with DFD arm for VPC was demonstrated over MET arm for both the safety and effectiveness end points.

Use of flecainide in combination antiarrhythmic therapy in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Antiarrhythmic therapy is commonly used for suppression of arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) in conjunction with implantable cardioverter-defibrillators and catheter ablation. The efficacy of combination flecainide and sotalol/metoprolol therapy for patients refractory to single agents and/or catheter ablation has not been well established. OBJECTIVE: The purpose of this study was to describe our experience with the addition of flecainide in combination with sotalol/metoprolol for treatment of arrhythmias in patients with ARVC. METHODS: We reviewed all patients within our genetic arrhythmia program with a definite diagnosis of ARVC (45 patients) and identified 8 patients treated with a combination of flecainide with sotalol/metoprolol after failure of single-agent therapy and/or catheter ablation. These patients were monitored with at least yearly clinic visits and device interrogations focused on the detection of major ventricular arrhythmias. RESULTS: Of the 8 patients reviewed, 6 demonstrated excellent arrhythmia control after initiation of combination therapy with flecainide and sotalol/metoprolol. These patients have been arrhythmia-free for an average of 35.5 months. Two patients have demonstrated recurrent arrhythmias despite combination therapy and have undergone repeat epicardial and endocardial ablation. Recurrence was noted to occur within 2 months of therapy. Patients were diverse with regard to the severity of disease as well as in the presence of genetic mutations. CONCLUSION: The addition of flecainide in combination with sotalol/metoprolol may be an effective antiarrhythmic strategy for the control of ventricular arrhythmias in patients with ARVC refractory to single-agent therapy and/or catheter ablation.

Promising approach for the preclinical assessment of cardiac risks using left ventricular pressure-volume loop analyses in anesthetized monkeys.

INTRODUCTION: Load-independent cardiac parameters obtained from the ventricular pressure-volume relationship are recognized as gold standard indexes for evaluating cardiac inotropy. In this study, for better analyses of cardiac risks, load-independent pressure-volume loop parameters were assessed in addition to load-dependent inotropic, hemodynamic and electrocardiographic changes in isoflurane-anesthetized monkeys. METHODS: The animals were given milrinone (a PDE 3 inhibitor), metoprolol (a ß-blocker), or dl-sotalol (a ß+IKr blocker) intravenously over 10min at two dose levels including clinically relevant doses (n=5/drug). RESULTS: Milrinone and metoprolol produced positive and negative inotropy, respectively. These effects were detected as changes in the slope of the preload-recruitable stroke work, which is a load-independent inotropic parameter. However, dl-sotalol did not alter the slope of the preload-recruitable stroke work. That means dl-sotalol produced no inotropy, although it decreased load-dependent inotropic parameters, including maximal upstroke velocity of left ventricular pressure, attributable to decreased heart rate and blood pressure. Other typical pharmacological effects of the compounds tested were also detected. Both ß-blockers produced PR prolongation, decreased left ventricular end-systolic pressure, increased left ventricular end-diastolic pressure, and increased maximal descending velocity of left ventricular pressure and time constant for isovolumic relaxation. dl-Sotalol also prolonged heart-rate-corrected QT interval. Milrinone induced reflex tachycardia, PR shortening, and decreased left ventricular end-diastolic pressure. DISCUSSION: The overall assessment by not only load-dependent inotropic parameters but also load-independent parameters obtained from the ventricular pressure-volume loop analysis using monkeys can provide further appropriate information for the assessment of drug-induced cardiac risks.

Marked hypertriglyceridemia in a woman receiving metoprolol succinate.

ß-blockers are commonly used therapies after acute myocardial infarction and in the management of congestive heart failure and hypertension. We report a case of a middle-aged woman with a history of mild hypertension who was placed on metoprolol succinate. Before initiation of the ß-blocker, her triglyceride level was in the borderline-high range (150-199 mg/dL). On treatment, her triglyceride levels exceeded 1000 mg/dL. She developed fatigue and mild abdominal discomfort but without biochemical evidence of pancreatitis. After discontinuation of metoprolol succinate, her triglyceride levels receded. This case illustrates an uncommon side effect with a very commonly used therapy in clinical practice. Clinicians should closely evaluate medications and/or other therapies in patients presenting with new-onset hypertriglyceridemia especially when levels are sufficiently elevated to pose increased risk of pancreatitis.

Ivabradine in combination with metoprolol succinate in the treatment of inappropriate sinus tachycardia.

BACKGROUND: Inappropriate sinus tachycardia (IST) is a clinical syndrome characterized by excessive resting heart rate (HR) or a disproportional increase in HR during exercise. ß-blocker or calcium channel-blocker therapy is often noneffective or not well tolerated. The HR reduction on ivabradine is similar to ß-blockers but in some patients its efficacy to resolve all IST-related symptoms is limited. The aim of the study was to assess the efficacy and safety of combining ivabradine with metoprolol succinate in patients with refractory highly symptomatic IST. METHODS: Twenty patients (36 ± 10 years; 16 women) with IST were enrolled. All patients received metoprolol succinate 95 mg single dose during the first month of the study. After 4 weeks of treatment with metoprolol, ivabradine was administered as adjuvant therapy up to 7.5 mg twice daily. Holter monitoring and treadmill stress test were performed at baseline, after 4, and 8 weeks of the study, respectively. RESULTS: We observed significant and similar reduction in resting HR both for metoprolol and for combined therapy compared to the baseline. The mean HR during daily activity was significantly lower on ivabradine and metoprolol compared to monotherapy with ß-blocker. The combined treatment yielded a significant increase in exercise capacity as assessed by treadmill stress test. After 4 weeks of combined therapy a significant reduction in IST-related symptoms, measured by means of the European Heart Rhythm Association score, was observed. CONCLUSION: Combining ivabradine with metoprolol is an effective and well-tolerated treatment option for IST in patients with refractory to monotherapy.

Hospitalization rates of generic metoprolol compared with the original beta-blocker in an epidemiological database study.

PURPOSE: A less favourable galenic profile of generic formulations of the beta-blocker metoprolol raised the concern of a higher risk for serious cardiovascular (CV) events. We assessed hospital admission rates for CV diseases and prescription prevalences of various drugs using claims data of statutory health insurances (SHIs) to compare the incidence of serious CV events among users of original and generic metoprolol. Index events included hospitalization due to myocardial infarction, hypertensive crisis and stroke. METHODS: Data files of three SHIs were linked with dispensing data of drug prescriptions from each pharmacy's electronic data processing centre on an individual basis. Incidences of hospital admissions among patients receiving original metoprolol and among patients treated with the generic equivalent were compared by logistic regression, stratified for Bremen and the rest of Northern Germany. Risk estimates and confidence intervals were adjusted for confounders. RESULTS: A total of 49,673 patients receiving metoprolol were identified within a cohort of 3,649,285 insurance members. While the crude analysis revealed a higher risk for index events in patients receiving the generic drug (Bremen: RR 1.45; Northern Germany: RR 1.14), no elevated risk remained after confounder adjustment (Bremen: OR 1.06; Northern Germany: OR 1.04). Among co-morbid conditions considered as confounders, a previous CV event and an elevated thromboembolic risk exerted the strongest effect on index events. CONCLUSIONS: SHI data are a valuable source for pharmacoepidemiology and health services research in Germany. Incidence rates of serious CV events did not reveal any noticeable differences between the original and the generic group after confounder adjustment.

Effectiveness and tolerability of acupuncture compared with metoprolol in migraine prophylaxis.

OBJECTIVES: In a randomized controlled multicenter trial extending over 24 weeks, we investigated whether acupuncture is as effective and safe as metoprolol in the prophylactic treatment of migraine under conditions similar to routine care. METHODS: One hundred fourteen migraine patients could be randomized to treatment over 12 weeks either with acupuncture (8 to 15 sessions) or metoprolol (100 to 200 mg daily). Main outcome measure was the difference in the number of migraine days between baseline and the weeks 9 to 12 after randomization (derived from a headache diary). RESULTS: Two of 59 patients randomized to acupuncture withdrew prematurely from the study compared to 18 of 55 randomized to metoprolol. The number of migraine days decreased by 2.5 +/- 2.9 days (baseline 5.8 +/- 2.5 days) in the acupuncture group compared to 2.2 +/- 2.7 days (baseline 5.8 +/- 2.9 days) in the metoprolol group (P= .721). The proportion of responders (reduction of migraine attacks by > or =50%) was 61% for acupuncture and 49% for metoprolol. Both physicians and patients reported fewer adverse effects in the acupuncture group. CONCLUSIONS: Due to missing the recruitment target (480 patients) and the high drop-out in the metoprolol group the results must be interpreted with caution. Still, they suggest that acupuncture might be an effective and safe treatment option for patients unwilling or unable to use drug prophylaxis.

The role of the new beta-blockers in treating cardiovascular disease.

The beta-adrenergic receptor blockers play an important role in the management of cardiovascular disease, including hypertension and chronic heart failure. However, concerns regarding safety and tolerability with currently available agents can limit their use. The beta-blockers vary with regard to several pharmacologic properties, including beta1/beta2 selectivity, intrinsic sympathomimetic activity, and, with the newest beta-blockers, vasodilation. These pharmacologic differences may result in clinically important differences in tolerability and hemodynamic properties. Nebivolol is a novel beta-blocker with both a greater degree of selectivity for beta1-adrenergic receptors than other agents in this class and an ability to stimulate endothelial nitric oxide production, leading to vasodilation and other potential clinical effects. Published randomized, controlled, multicenter studies with nebivolol have shown that once-daily treatment significantly reduces systolic and diastolic blood pressure in patients with mild-to-moderate hypertension, compared with placebo, in a dose-dependent manner, and is well tolerated, with an adverse event profile similar to that of placebo. When compared with other beta-blockers as well as with other antihypertensive classes of agents in head-to-head trials, nebivolol demonstrated similar antihypertensive efficacy and a lower incidence of adverse events. Nebivolol has also been shown to significantly reduce morbidity and mortality in a large population of elderly patients with chronic heart failure, independent of left ventricular ejection fraction. Nebivolol is currently available in Europe for the management of hypertension and is expected to be available soon in the United States.

[Assessment of the efficacy and tolerance of delayed-action nifedipine as the monotherapy or in combination with metoprolol in patients with arterial hypertension]. / Otsenka éffektivnosti i perenosimosti nifedipina prolongirovannogo deistviia v vide monoterapii i v kombinatsii s metoprololom u bol'nykh arterial'noi gipertoniei.

AIM: To compare efficacy and safety of nifedipin-retard (cordaflex-retard, Egis, Hungary) used in monotherapy and in combination with metoprolol (egilok, Egis, Hungary) in patients with arterial hypertension (AH). MATERIAL AND METHODS: The study included 20 patients with AH stage I-II (12 males, 8 females, mean age 57.3 years, mean duration of the disease 8.6 years). Nifedipin-retard was given in a daily dose 40 mg/day (20 mg twice a day) in monotherapy and 20 mg/day in combination with metoprolol which was administered 50 mg twice a day (a daily dose 100 mg/day). The control examination consisted of a physical examination, measurement of arterial pressure (AP) by Korotkov, registration of heart rate, ECG, 24-h AP monitoring, echocardiography. RESULTS: By 24-h AP monitoring, a 4-week treatment with nifedipin-retard alone resulted in lowering of systolic arterial pressure. The combined treatment produced a more pronounced fall both in systolic and diastolic pressure. Diastolic left-ventricular function improved in combined therapy. Side effects observed in nifedipin-retard monotherapy got much more weaker when this drug combined with metoprolol. CONCLUSION: Combination of nifedipin-retard with metoprolol provides better clinical response and tolerance than monotherapy with nifedipin-retard.

Nifedipine, captopril, metoprolol and nifedipine with metoprolol in hypertensive crisis in non-intensive care setting.

In 102 cases of severe hypertension (DBP > or = 115 mm Hg), with or without acute complications, efficacy and safety of SL Nifedipine 10 mg (NIF), SL Captopril 25 mg (CAP), IV Metoprolol 15 mg (MET) and SL NIF + IV MET were studied in an inpatient trial. Maximum mean percent reduction in SBP was 13.3, 9.7, 15.7 and 19.9 and in DBP was 21.2, 13.9, 12.5 and 20.4 with NIF, CAP, MET and NIF + MET respectively. A safe DBP of < or = 110 mm Hg (Kaplan) was achieved in 90, 61, 72.2 and 95.2 percent of patients. A statistically significant fall in DBP was observed at 5 minutes with all regimens except CAP which was at 15 minutes. Mild side effects observed were palpitations and flushing (NIF n = 4), taste disturbances (CAP n = 3), heaviness of head (CAP n = 1) and giddiness (MET n = 2, NIF + MET n = 2). The trial data suggest that hypertensive crisis can be managed, without intensive care facility, with all four regimens; this implies significant cost containment.

[Effects of calcium antagonists on withdrawal of beta-receptor blockers in rats during left ventricular hypertrophy].

The hemodynamic changes of metoprolol (Met, 50 mg.kg-1.d-1, po, 3 wk) withdrawal for 1 day and the effects of nifedipine (Nif) and m-nifedipine (m-Nif) on these changes were observed in pressure overload hypertrophy in rats by abdominal aortic constriction for 4 wk. Both Nif and m-Nif (10 mg.kg-1.d-1, respectively, po, 3 wk) significantly attenuated the increase of MAP (from 14.3 +/- 2.3 to 12.9 +/- 2.3 and 11.3 +/- 2.4 kPa, respectively, n = 6-7, P < 0.05) and decrease the abnormal development of systolic function of left ventricle after Met withdrawal. Radioreceptor assay indicates that Nif and m-Nif can prevent the up-regulation of myocardium beta-receptors in left ventricular hypertrophy and large dose of Met exposure for a long time. These results suggest that calcium antagonists administered with beta-blockers can prevent beta-receptor blocker withdrawal syndrome.

Addition of urapidil or metoprolol to the treatment of hypertensive non-responders to nifedipine monotherapy: efficacy and metabolic effects. Italian Urapidil Study Group.

This study compared the effects on blood pressure and some metabolic variables of a 3-month period addition therapy of urapidil or metoprolol in 273 hypertensive non-responders to nifedipine sustained release (SR) monotherapy. This was a randomised, open-label, controlled, parallel-group comparative study, followed by another 3-month period during which all patients received the combination nifedipine SR-urapidil independently of the treatment they were previously randomized to. Both treatments caused significant falls in systolic (SBP) and diastolic blood pressure (DBP) when compared with the nifedipine SR monotherapy phase. The addition of urapidil to nifedipine SR caused a significant blood pressure reduction of 16.6/13.6 mmHg (p < 0.001), whereas after metoprolol the decrease was of 15.1/14 mmHg (p < 0.001). While in the overall population there was no statistically significant difference between the reduction caused by the two antihypertensive agents added to nifedipine SR, significant differences (DBP, p < 0.05; SBP, p < 0.01) were observed in the group of 51 patients aged at least 60 years. Total cholesterol and LDL-cholesterol were significantly reduced (p < 0.001) after the addition of urapidil to nifedipine SR, while, on the contrary, the addition of metoprolol to nifedipine SR was followed by a significant rise (p = 0.001). The changes caused by the two agents were statistically different among them (p < 0.01). The non-atherogenic HDL-cholesterol did not change during the addition of urapidil or metoprolol to nifedipine SR, while, the HDL/total cholesterol ratio was significantly increased after the addition of urapidil (p < 0.01) and unmodified after the addition of metoprolol. Between-group analysis showed a significant difference (p = 0.005). Serum triglycerides did not change in the urapidil plus nifedipine SR group but significantly increased in the metoprolol plus nifedipine SR group (p < 0.001); between-group difference was not statistically significant. Plasma glucose was unchanged after the addition of urapidil whereas it was significantly (p < 0.001) increased in the metoprolol-added group with a between-group difference statistically significant (p < 0.05). When metoprolol was substituted by urapidil during the second 3-month period, the negative effects on glucose, total cholesterol, LDL cholesterol and triglycerides were abolished while in the group already treated with urapidil plus nifedipine SR the favourable effects of urapidil plus nifedipine SR on total cholesterol, LDL-cholesterol and HDL/total cholesterol ratio were significantly increased compared with the end of the first 3-month treatment. The results of this study show that when urapidil and metoprolol are added to non-responders to nifedipine SR therapy there is a clinically and statistically relevant blood pressure reduction with both agents, with a therapeutic advantage for the combination urapidil + nifedipine SR in patients more than 60 years old. Moreover, the addition of urapidil was associated with a more favourable effect on serum lipids and glucose than that produced by the addition of metoprolol.

Acupuncture versus metoprolol in migraine prophylaxis: a randomized trial of trigger point inactivation.

OBJECTIVES: To compare the effects of dry needling of myofascial trigger points in the neck region to metoprolol in migraine prophylaxis. DESIGN: Randomized, group comparative study. patients, investigator and statistician were blinded as to treatment, the therapist was blinded as to results. SETTING: Outpatient pain clinic in the northern Copenhagen area. Patients were referred by general practitioners or respondents to newspaper advertisements. SUBJECTS: Included were patients with a history of migraine with or without aura for at least 2 years. Excluded were persons with contraindications against treatment with beta blockers, chronic pain syndromes, pregnancy or previous experience with acupuncture or beta-blocking agents. A total of 85 patients were included; 77 completed the study. INTERVENTIONS: After a 4-week run-in period, patients were allocated to a 17-week regimen either with acupuncture and placebo tablets or to placebo stimulation and metoprolol 100 mg daily. RESULTS: Both groups exhibited significant reduction in attack frequency (P < 0.01). No difference was found between the groups regarding frequency (P > 0.20) or duration (P > 0.10) of attacks, whereas we found a significant difference in global rating of attacks in favour of metoprolol (P < 0.05). CONCLUSIONS: Trigger point inactivation by dry needling is a valuable supplement to the list of migraine prophylactic tools, being equipotent to metoprolol in the influence on frequency and duration (but not severity) of attacks, and superior in terms of negative side-effects.

The long-term effects of metoprolol and epanolol on tissue-type plasminogen activator and plasminogen activator inhibitor 1 in patients with ischaemic heart disease.

This double-blind, randomized parallel group study investigated the effect of 6 months beta-adrenoceptor antagonist therapy with either metoprolol (beta 1-selective without intrinsic sympathomimetic activity [ISA]) or epanolol (beta 1-selective with ISA) on markers of endogenous fibrinolysis in 20 patients with chronic stable angina receiving concurrent treatment with nifedipine. Neither drug had an effect on tissue-type plasminogen activator or plasminogen activator inhibitor type 1 (PAI-1). A significant correlation between fasting insulin and PAI-1 has previously been described and was confirmed in this study. The group treated with metoprolol showed a significant rise in fasting insulin after 6 months with no change in PAI-1. This suggests that the previously described link between these two may not be causal.

Antihypertensive efficacy and side effects of three beta-blockers and a diuretic in elderly hypertensives: a report from the STOP-Hypertension study.

OBJECTIVE: To compare the blood pressure-lowering efficacy, the frequency of side effects and changes in laboratory values of three beta-blockers and a potassium-sparing diuretic combination in elderly hypertensive patients. DESIGN: The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. METHODS: The study group consisted of 1627 elderly hypertensive patients (mean +/- SD age 75.7 +/- 3.7 years; 37% males, 63% females). Supine and standing blood pressure, heart rate and side effects were recorded at each visit. Blood was drawn for routine analysis. The mean length of follow-up was 25 months (range 6-65). No patient was lost to follow-up. RESULTS: After 2-months' single-drug therapy, all four active drugs were found to be equally effective in reducing diastolic blood pressure (DBP). However, there were differences in their efficacy in reducing systolic blood pressure (SBP); the diuretic was significantly more effective than the beta-receptor blockers. The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate. More than two-thirds of the patients were given supplementary treatment, most of them already by the 2-month visit, after which there was no significant difference in blood pressure among the treatment regimens. The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens. CONCLUSION: Metoprolol (controlled release), atenolol, pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP. There were differences in their efficacy in reducing SBP, the diuretic being more effective than the beta-blockers. After addition of supplementary treatment (beta-blocker to diuretic, or vice versa) there were no significant differences in blood pressure reduction among the groups. The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens. Thus, the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs.

Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine.

The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week treatment with a beta blocker (metoprolol CR, 200 mg once daily) or a dihydropyridine calcium antagonist (nifedipine retard 20 mg twice daily) were then compared according to a double-blind, parallel group design. Metoprolol significantly reduced the number and duration of the ischemic episodes during daily life (p less than 0.05) irrespective of the patients' clinical characteristics. Nifedipine was ineffective, particularly in patients with angina predominantly on effort and with a moderate to severe reduction in exercise tolerance. It is concluded that in patients with mixed angina, ischemic episodes during daily life are more likely to occur in patients with a clinical presentation suggesting poor coronary reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of hypertension in elderly patients with felodipine and metoprolol: a double-blind, placebo-controlled clinical trial.

1. Forty-nine patients aged 65-80 years, whose Phase V diastolic blood pressure (dBP) was above 95 mmHg after 4 weeks open treatment with metoprolol 50 mg twice daily were randomized to receive, double-blind, the calcium antagonist felodipine (n = 32) 2.5 mg twice daily or placebo (n = 17) in addition to metoprolol for 2 weeks. If the dBP remained greater than 95 mmHg, the dose of felodipine or placebo was doubled for a further 2 weeks; if the dBP was still greater than 95 mmHg, the dose of felodipine was doubled again to 10 mg twice daily or the corresponding placebo dose given. The duration of the double-blind period was 6 weeks, all patients receiving metoprolol 50 mg twice daily throughout. 2. At the end of the double-blind period, the seated dBP was reduced from 103 +/- 5 (mean +/- s.d.) to 88 +/- 7 mmHg (P less than 0.001) by felodipine and from 105 +/- 100 +/- 11 mmHg (NS) by placebo. The differences between these reductions (P less than 0.01) and between the final dBPs (P less than 0.001) were significant. Eighty-nine per cent of patients receiving felodipine and 33% of those receiving placebo (P less than 0.001) had controlled (dBP less than or equal to 95 mmHg) BPs. Half (14/27 completing) of the patients receiving felodipine required 2.5 mg throughout; 9/27 needed 5 mg and 4/27 10 mg twice daily. Adverse events occurred with equal frequency in the two groups, but the profile was different.(ABSTRACT TRUNCATED AT 250 WORDS)

Slow-release metoprolol and nifedipine in essential hypertension: 24 hour noninvasive ambulatory blood pressure monitoring.

To assess the efficacy and tolerability of metoprolol (MET), 200 mg slow release (SR) q.d., and nifedipine (NIF), 20 mg SR b.i.d., 20 mildly to moderately hypertensive outpatients (14 men and 6 women; mean age 41.5 years, range 27-49 years) were studied. After being withdrawn from previous antihypertensive treatments, the patients were given single-blind placebo for 2 weeks and thereafter, in double-blind, randomized sequence, MET and NIF, both for 2 weeks. At the end of each period of the study, blood pressure (BP) was recorded for 24 h using a noninvasive ambulatory BP monitoring device (ICR System) with readings taken every 10 min (from 6 a.m. to 6 p.m.), 15 min (from 6 to 12 p.m.), and 20 min (from 12 p.m. to 6 a.m.). Five patients did not complete the study because of the occurrence of unwanted effects (one patient on MET and four patients on NIF). In the 15 patients who concluded the study both drugs significantly reduced (p less than 0.01), in comparison with placebo, systolic BP (SBP), mean arterial pressure (MAP), and diastolic BP (DBP) throughout the 24 h (MET: -16.9, -11.5, and -8.9 mm Hg; NIF: -12.7, -8.4, and -6.6 mm Hg, respectively). In comparison with NIF, SBP and MAP but not DBP were significantly reduced by MET (p less than 0.01 and p less than 0.05, respectively). We conclude that in our patient population MET was more effective and better tolerated than NIF. A possible explanation could be the relatively young age of the subjects we studied.

Nifedipine and metoprolol in unstable angina: findings from the Holland Interuniversity Nifedipine/Metoprolol Trial (HINT).

We conducted a multicenter, double-blind, placebo-controlled, randomized trial of nifedipine, metoprolol, and their combination in 338 patients whose hospital admission diagnosis was unstable angina and who were not pretreated with a beta-blocker, and of nifedipine in 177 patients who were treated with a beta-blocker. The main outcome event was the recurrence of ischemia or progression to myocardial infarction within 48 h. Trial medication effects are expressed as ratios of event rates relative to placebo, e.g., the ratio for nifedipine is the event rate under nifedipine divided by that under placebo. In addition, 95% confidence intervals are given. In patients not pretreated with a beta-blocker, the event rate ratio for nifedipine was 1.15 (0.83, 1.64), for metoprolol 0.76 (0.49, 1.16), and for the combination 0.80 (0.53, 1.19). In patients already on a beta-blocker, the addition of nifedipine was favorable; i.e., the rate ratio was 0.68 (0.47, 0.97). Equal numbers of patients developed myocardial infarction and reversible ischemia. Most infarctions occurred early, within 6 h of randomization. In patients not already on a beta-blocker, the nifedipine rate ratio for infarction was 1.51 (0.87, 2.74). These results suggest that, in patients not on previous beta-blockade, metoprolol has a beneficial short-term effect on unstable angina, a fixed combination with nifedipine provides no further gain, and nifedipine may be ineffective or counterproductive. On the other hand, the addition of nifedipine to existing beta-blockade when the patient becomes unstable seems beneficial.